DESCRIPTION: Asymmetrical cell division and protein localization is a fundamental process in eukaryotic and prokaryotic cells. The neural precursor cell division in Drosophila serves as a model system for studying the mechanisms of asymmetric cell division in general. In this system, both genes responsible for establishing cellular polarity and genes playing specific roles in direct protein localization are required for the asymmetric distribution of cell fate determinants, such as Numb. The goal of this proposal is to address the function of I3, a candidate component of the cellular machinery that is localizing Numb. The consequences of loss-or gain-of I3 function will be assessed by isolating I3 mutants and by ectopically expressing I3. The relationship between I3 and genes known to participate in asymmetric cell division will be established by molecular epistasis analysis. Structure-function analysis will uncovered the domain responsible for the asymmetric localization of I3 and test the functioning of Numb-I3 interaction. By isolating proteins that associate with I3, additional components involved in the process will be identified. This will provide us with a broader view of how cellular symmetry is established and how asymmetric protein localization is accomplished. It is expected that studying asymmetric cell divisions in Drosophila will advance our understanding of stem cell divisions in humans and lead to therapeutic inventions in the treatment of cancer and neurodegenerative diseases.